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Draft Assessment Report on Chelidonium Majus L., Herba

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Draft Assessment Report on Chelidonium Majus L., Herba 25 November 2010 EMA/HMPC/369801/2009 Committee on Herbal Medicinal Products (HMPC) Assessment report on Chelidonium majus L., herba Based on Article 10a of Directive 2001/83/EC as amended (well-established use) Based on Article 16d(1), Article 16f and Article 16h of Directive 2001/83/EC as amended (traditional use) Draft Herbal substance(s) (binomial scientific name of Chelidonium majus L. the plant, including plant part) Dried whole or cut aerial parts of the plant Herbal preparation(s) Internal Use a) Chelidonii herba: comminuted b) Chelidonii tincture: 1:10 ethanol 45% (V/V) c) Chelidonii extractum fluidum: 1:1 ethanol 25% (V/V) d) Chelidonii extractum siccum (concentration not specified) e) Chelidonium majus mother tincture (M.T. (ø)) External Use a) Eye-drops: (preparation not specified) b) Ointment: (concentration not specified) Pharmaceutical forms Herbal preparation in solid or liquid dosage form or as a herbal tea for oral use. Herbal preparation in solid or liquid dosage form for external use. Rapporteur Assessor(s) 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7051 E-mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged. Note: This Assessment Report is published to support the release for public consultation of the draft Community herbal monograph on Chelidonium majus L. It should be noted that this document is a working document, not yet fully edited, and which shall be further developed after the release for consultation of the monograph. Interested parties are welcome to submit comments to the HMPC secretariat, which the Rapporteur and the MLWP will take into consideration but no ‘overview of comments received during the public consultation’ will be prepared in relation to the comments that will be received on this assessment report. The publication of this draft assessment report has been agreed to facilitate the understanding by Interested Parties of the assessment that has been carried out so far and led to the preparation of the draft monograph. Assessment report on Chelidonium majus L., herba EMA/HMPC/369801/2009 Page 2/30 Table of contents Table of contents ...................................................................................................................3 1. Introduction.......................................................................................................................5 1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof .5 1.2. Information about products on the market in the Member States ............................ 10 2. Non-Clinical Data .............................................................................................................12 2.1. Pharmacology.................................................................................................. 12 2.1.1. Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof.............................................................................. 12 2.1.2. Assessor’s overall conclusions on pharmacology................................................. 20 2.2. Pharmacokinetics ............................................................................................. 21 2.2.1. Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof.............................................................................. 21 2.2.2. Assessor’s overall conclusions on pharmacokinetics ............................................ 22 2.3. Toxicology....................................................................................................... 22 2.3.1. Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof .......................................................................................... 22 2.3.2. Assessor’s overall conclusions on toxicology ...................................................... 23 3. Clinical Data.....................................................................................................................24 3.1. Clinical Pharmacology ....................................................................................... 24 3.1.1. Pharmacodynamics........................................................................................ 24 3.1.1.1. Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity. ..................................... 24 3.1.1.2. Assessor’s overall conclusions on pharmacodynamics....................................... 24 3.1.2. Pharmacokinetics .......................................................................................... 24 3.1.2.1. Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity. ..................................... 24 3.1.2.2. Assessor’s overall conclusions on pharmacokinetics ......................................... 24 3.2. Clinical Efficacy ................................................................................................ 24 3.2.1. No dose-finding studies. ................................................................................. 24 3.2.2. Clinical studies (case studies and clinical trials).................................................. 24 3.2.3. Clinical studies in special populations (e.g. elderly and children)........................... 26 3.2.4. Assessor’s overall conclusions on clinical efficacy ............................................... 26 3.3. Clinical Safety/Pharmacovigilance....................................................................... 26 3.3.1. Patient exposure ........................................................................................... 26 3.3.2. Adverse events ............................................................................................. 27 3.3.3. Serious adverse events and deaths .................................................................. 29 3.3.4. Laboratory findings........................................................................................ 29 3.3.5. Safety in special populations and situations....................................................... 29 3.3.5.1. Intrinsic (including elderly and children) /extrinsic factors................................. 29 3.3.5.2. Drug interactions ........................................................................................ 29 3.3.5.3. Use in pregnancy and lactation ..................................................................... 29 3.3.5.4. Overdose................................................................................................... 29 3.3.5.5. Drug abuse................................................................................................ 29 3.3.5.6. Withdrawal and rebound.............................................................................. 29 3.3.5.7. Effects on ability to drive or operate machinery or impairment of mental ability ... 29 Assessment report on Chelidonium majus L., herba EMA/HMPC/369801/2009 Page 3/30 3.3.6. Assessor’s overall conclusions on clinical safety ................................................. 29 4. Overall conclusions ............................................................................................. 30 Assessment report on Chelidonium majus L., herba EMA/HMPC/369801/2009 Page 4/30 1. Introduction 1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof Herbal substance(s) Chelidonium majus L. The European Pharmacopoeia (01/2008:1861) monograph Chelidonii herba provides the following definition: dried, whole or cut aerial parts of Chelidonium majus L. collected during flowering. Content: minimum 0.6 per cent of total alkaloids, expressed as chelidonine (C20H19NO5; Mr 353.4) (dried drug). Chelidonium majus L. is known under the synonyms: English: greater celandine, devil’s milk, rock poppy, tetterwort, swallow-wort Italian: celidonia, erba di porri, cinerognola, erba maistra, erba nocca German: Schöllkraut, Schellkraut, Schwalbenkraut, Goldwurz, Blutkraut, Gelbes Millkraut French: chélidoine, herbe d’éclaire, herbe de l’hirondelle, felougue, herbes de Sainte Claire, herbe hirondalle Dutch: stinkende gouwe Spanish: celidonia Portugal: celidonia Polish: ziele glistnika, złotnik, jaskółcze ziele, glistnik pospolity There are over 20 different Chelidonium alkaloids identified. Here are the different groups of chemical molecules who are present in the herb of Chelidonium majus (Barnes et al, 2007; Bruneton, 1999) Benzylisoquinoline type (0.01-1%): with at least three subgroups, Benzophenanthridines: chelerythrine, chelidonine, sanguinarine, isochelidonine Protoberberines: berberine, coptisine, dihydrocoptisine, stylopine Protopine Acids: chelidonic, malic, citric, caffeic (0.4%) ferulic (0.02%), p-coumaric (0.06%), gentisic and p- hydroxybenzoic acids Hydroxycinnamic acid derivates: (-)-2-(E)-caffeoyl-D-glyceric acid, (-)-4-(E)-caffeoyl-L- threonic acid, (-)-(2)-(E)-coffeoyl threonic acid lactone, (+)-(E)-caffeoyl-L-malic acid Others: a saponine, carotenoids, a phytocytostatin (chelidocystatin), sparteine and flavonoids. Chelidonium majus L. belongs to the family of the Papaveracecae and
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